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104 results on '"Iacono, W.G."'

1. Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study

Author

Lisdahl, Krista M., Tapert, Susan, Sher, Kenneth J., Gonzalez, Raul, Nixon, Sara Jo, Feldstein Ewing, Sarah W., Conway, Kevin P., Wallace, Alex, Sullivan, Ryan, Hatcher, Kelah, Kaiver, Christine, Thompson, Wes, Reuter, Chase, Bartsch, Hauke, Wade, Natasha E., Jacobus, Joanna, Albaugh, M.D., Allgaier, N., Anokhin, A.P., Bagot, K., Baker, F.C., Banich, M.T., Barch, D.M., Baskin-Sommers, A., Breslin, F.J., Brown, S.A., Calhoun, V., Casey, B.J., Chaarani, B., Chang, L., Clark, D.B., Cloak, C., Constable, R.T., Cottler, L.B., Dagher, R.K., Dapretto, M., Dick, A., Do, E.K., Dosenbach, N.U.F., Dowling, G.J., Fair, D.A., Florsheim, P., Foxe, J.J., Freedman, E.G., Friedman, N.P., Garavan, H.P., Gee, D.G., Glantz, M.D., Glaser, P., Gonzalez, M.R., Gray, K.M., Grant, S., Haist, F., Hawes, S., Heeringa, S.G., Hermosillo, R., Herting, M.M., Hettema, J.M., Hewitt, J.K., Heyser, C., Hoffman, E.A., Howlett, K.D., Huber, R.S., Huestis, M.A., Hyde, L.W., Iacono, W.G., Isaiah, A., Ivanova, M.Y., James, R.S., Jernigan, T.L., Karcher, N.R., Kuperman, J.M., Laird, A.R., Larson, C.L., LeBlanc, K.H., Lopez, M.F., Luciana, M., Luna, B., Maes, H.H., Marshall, A.T., Mason, M.J., McGlade, E., Morris, A.S., Mulford, C., Nagel, B.J., Neigh, G., Palmer, C.E., Paulus, M.P., Pecheva, D., Prouty, D., Potter, A., Puttler, L.I., Rajapakse, N., Ross, J.M, Sanchez, M., Schirda, C., Schulenberg, J., Sheth, C., Shilling, P.D., Sowell, E.R., Speer, N., Squeglia, L., Sripada, C., Steinberg, J., Sutherland, M.T., Tomko, R., Uban, K., Vrieze, S., Weiss, S.R.B., Wing, D., Yurgelun-Todd, D.A., Zucker, R.A., and Heitzeg, Mary M.

Published
2021
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3. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Author

Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., Fisher, S.E., Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., and Fisher, S.E.

Abstract

Item does not contain fulltext

Published
2022

4. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, M.A. Johnson, E.C. Chou, Y.-L. Coleman, J.R.I. Thornton, L.M. Walters, R.K. Yilmaz, Z. Baker, J.H. Hübel, C. Gordon, S. Medland, S.E. Watson, H.J. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Berrettini, W.H. Boehm, I. Boni, C. Boraska Perica, V. Buehren, K. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. Davis, O.S.P. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo, E. Duncan, L.E. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M.M. Fischer, K. Föcker, M. Foretova, L. Forstner, A.J. Forzan, M. Franklin, C.S. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacos Mayora, M. Guillaume, S. Guo, Y. Hakonarson, H. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Huckins, L.M. Hudson, J.I. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Julià, A. Kalsi, G. Kaminská, D. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Levitan, R.D. Li, D. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P.J. Maj, M. Mannik, K. Marsal, S. Marshall, C.R. Mattingsdal, M. McDevitt, S. McGuffin, P. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, K. Monteleone, A.M. Monteleone, P. Nacmias, B. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Pinto, D. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S.W. Schmidt, U. Schork, N.J. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op't Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Szatkiewicz, J.P. Tachmazidou, I. Tenconi, E. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Wagner, G. Walton, E. Widen, E. Zeggini, E. Zerwas, S. Zipfel, S. Bergen, A.W. Boden, J.M. Brandt, H. Crawford, S. Halmi, K.A. Horwood, L.J. Johnson, C. Kaplan, A.S. Kaye, W.H. Mitchell, J. Olsen, C.M. Pearson, J.F. Pedersen, N.L. Strober, M. Werge, T. Whiteman, D.C. Woodside, D.B. Grove, J. Henders, A.K. Larsen, J.T. Parker, R. Petersen, L.V. Jordan, J. Kennedy, M.A. Birgegård, A. Lichtenstein, P. Norring, C. Landén, M. Mortensen, P.B. Polimanti, R. McClintick, J.N. Adkins, A.E. Aliev, F. Bacanu, S.-A. Batzler, A. Bertelsen, S. Biernacka, J.M. Bigdeli, T.B. Chen, L.-S. Clarke, T.-K. Degenhardt, F. Docherty, A.R. Edwards, A.C. Foo, J.C. Fox, L. Frank, J. Hack, L.M. Hartmann, A.M. Hartz, S.M. Heilmann-Heimbach, S. Hodgkinson, C. Hoffmann, P. Hottenga, J.-J. Konte, B. Lahti, J. Lahti-Pulkkinen, M. Lai, D. Ligthart, L. Loukola, A. Maher, B.S. Mbarek, H. McIntosh, A.M. McQueen, M.B. Meyers, J.L. Milaneschi, Y. Palviainen, T. Peterson, R.E. Ryu, E. Saccone, N.L. Salvatore, J.E. Sanchez-Roige, S. Schwandt, M. Sherva, R. Streit, F. Strohmaier, J. Thomas, N. Wang, J.-C. Webb, B.T. Wedow, R. Wetherill, L. Wills, A.G. Zhou, H. Boardman, J.D. Chen, D. Choi, D.-S. Copeland, W.E. Culverhouse, R.C. Dahmen, N. Degenhardt, L. Domingue, B.W. Frye, M.A. Gäebel, W. Hayward, C. Ising, M. Keyes, M. Kiefer, F. Koller, G. Kramer, J. Kuperman, S. Lucae, S. Lynskey, M.T. Maier, W. Mann, K. Männistö, S. Müller-Myhsok, B. Murray, A.D. Nurnberger, J.I. Preuss, U. Räikkönen, K. Reynolds, M.D. Ridinger, M. Scherbaum, N. Schuckit, M.A. Soyka, M. Treutlein, J. Witt, S.H. Wodarz, N. Zill, P. Adkins, D.E. Boomsma, D.I. Bierut, L.J. Brown, S.A. Bucholz, K.K. Costello, E.J. de Wit, H. Diazgranados, N. Eriksson, J.G. Farrer, L.A. Foroud, T.M. Gillespie, N.A. Goate, A.M. Goldman, D. Grucza, R.A. Hancock, D.B. Harris, K.M. Hesselbrock, V. Hewitt, J.K. Hopfer, C.J. Iacono, W.G. Johnson, E.O. Karpyak, V.M. Kendler, K.S. Kranzler, H.R. Krauter, K. Lind, P.A. McGue, M. MacKillop, J. Madden, P.A.F. Maes, H.H. Magnusson, P.K.E. Nelson, E.C. Nöthen, M.M. Palmer, A.A. Penninx, B.W.J.H. Porjesz, B. Rice, J.P. Rietschel, M. Riley, B.P. Rose, R.J. Shen, P.-H. Silberg, J. Stallings, M.C. Tarter, R.E. Vanyukov, M.M. Vrieze, S. Wall, T.L. Whitfield, J.B. Zhao, H. Neale, B.M. Wade, T.D. Heath, A.C. Montgomery, G.W. Martin, N.G. Sullivan, P.F. Kaprio, J. Breen, G. Gelernter, J. Edenberg, H.J. Bulik, C.M. Agrawal, A.

Subjects
mental disorders
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors. © 2020 Society for the Study of Addiction

Published
2021

5. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Author

Quach, B.C., Bray, M.J., Gaddis, N.C., Liu, M., Palviainen, T., Minica, C.C., Zellers, S., Sherva, R., Aliev, F., Nothnagel, M., Young, K.A., Marks, J., Young, H., Guo, Y., Waldrop, A., Sey, N., Landi, M.T., McNeil, D.W., Farrer, L.A., Markunas, C.A., Vink, J.M., Hottenga, J.J., Iacono, W.G., Kranzler, H.R., Saccone, N.L., Neale, M.C., Madden, P.A.F., Rietschel, M., Marazita, M.L., McGue, M.K., Won, H., Winterer, G., Grucza, R.A., Dick, D.M., Gelernter, J., Caporaso, N.E., Baker, T.B., Boomsma, D.I., Kaprio, J., Hokanson, J.E., Vrieze, S., Bierut, L.J., Johnson, E.O., Hancock, D.B., Quach, B.C., Bray, M.J., Gaddis, N.C., Liu, M., Palviainen, T., Minica, C.C., Zellers, S., Sherva, R., Aliev, F., Nothnagel, M., Young, K.A., Marks, J., Young, H., Guo, Y., Waldrop, A., Sey, N., Landi, M.T., McNeil, D.W., Farrer, L.A., Markunas, C.A., Vink, J.M., Hottenga, J.J., Iacono, W.G., Kranzler, H.R., Saccone, N.L., Neale, M.C., Madden, P.A.F., Rietschel, M., Marazita, M.L., McGue, M.K., Won, H., Winterer, G., Grucza, R.A., Dick, D.M., Gelernter, J., Caporaso, N.E., Baker, T.B., Boomsma, D.I., Kaprio, J., Hokanson, J.E., Vrieze, S., Bierut, L.J., Johnson, E.O., and Hancock, D.B.

Abstract

Contains fulltext : 276901.pdf (Publisher’s version ) (Open Access), Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (rg = 0.40–1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking

Published
2020

6. The validity of the lie detector: two surveys of scientific opinion

Author

Iacono, W.G. and Lykken, D.T.

Subjects
Lie detectors and detection -- Research, Evidence (Law) -- Research, Psychologists -- Surveys, Psychology and mental health, Social sciences
Abstract

The widespread use of polygraph ('lie detector') tests has important social and individual consequences. Courts asked to admit polygraph findings into evidence, as well as individuals asked to submit to polygraph tests, have a natural interest in the acceptance by the relevant scientific community of the polygraph technique. For this reason, we conducted mail surveys to obtain the opinions of 2 groups of scientists from relevant disciplines: members of the Society for Psychophysiological Research and Fellows of the American Psychological Association's Division 1 (General Psychology). Survey return rates were high (91% and 74%, respectively). Most of the respondents believed that polygraphic lie detection is not theoretically sound, claims of high validity for these procedures cannot be sustained, the lie test can be beaten by easily learned countermeasures, and polygraph test results should not be admitted into evidence in courts of law.

Published
1997

8. A genetic epidemiological mega analysis of smoking initiation in adolescents

Author

Maes, H.H., Prom-Wormley, E., Eaves, L.J., Rhee, S.H., Hewitt, J.K., Young, S., Corley, R.P., McGue, M.K., Iacono, W.G., Legrand, L., Samek, D., Murrelle, E.L., Silberg, J.L., Miles, D., Schieken, R.M., Beunen, G.P., Thomis, M., Rose, R.J., Dick, D.M., Boomsma, D.I., Bartels, M., Vink, J.M., Lichtenstein, P., White, V., Kaprio, J., Neale, M.C., Maes, H.H., Prom-Wormley, E., Eaves, L.J., Rhee, S.H., Hewitt, J.K., Young, S., Corley, R.P., McGue, M.K., Iacono, W.G., Legrand, L., Samek, D., Murrelle, E.L., Silberg, J.L., Miles, D., Schieken, R.M., Beunen, G.P., Thomis, M., Rose, R.J., Dick, D.M., Boomsma, D.I., Bartels, M., Vink, J.M., Lichtenstein, P., White, V., Kaprio, J., and Neale, M.C.

Abstract

Item does not contain fulltext, Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N=19 313 pairs) between age 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the US, Europe and Australia. Results. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of smoking initiation across developed countries. The estimate of additive genetic contributions to liability of smoking initiation increased from approximately 15% to 45% from age 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to smoking initiation at age 13 (70%) and gradually less by age 19 (40%). Conclusions. Both additive genetic and shared environmental factors significantly contribute to variance in smoking initiation throughout adolescence. The present study, the largest genetic epidemiological study on smoking initiation to date, found consistent results across 11 studies for the etiology of smoking initiation. Environmental factors, especially those shared by siblings in a family, primarily influence smoking initiation variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. IMPLICATIONS: This is the first study to find evidence of genetic factors in liability to smoking initiation at ages as young as 12. It also shows the st

Published
2017

9. Genome-wide association meta- Analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Author

Sniekers, S. (Suzanne), Stringer, S. (Sven), Watanabe, K. (Kyoko), Jansen, P.R. (Philip), Coleman, J.R.I. (Jonathan R I), Krapohl, E. (Eva), Taskesen, E. (Erdogan), Hammerschlag, A.R. (Anke R.), Okbay, A. (Aysu), Zabaneh, D. (Delilah), Amin, N. (Najaf), Breen, G. (Gerome), Cesarini, D. (David), Chabris, C.F. (Christopher F), Iacono, W.G. (William), Ikram, M.A. (Arfan), Johannesson, M. (Magnus), Koellinger, P. (Philipp), Lee, J.J. (James J.), Magnusson, P.K. (Patrik), McGue, M. (Matt), Miller, M. (Mike), Ollier, W.E.R. (William), Payton, A. (Antony), Pendleton, N. (Neil), Plomin, R. (Robert), Rietveld, C.A. (Niels), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Posthuma, D. (Danielle), Sniekers, S. (Suzanne), Stringer, S. (Sven), Watanabe, K. (Kyoko), Jansen, P.R. (Philip), Coleman, J.R.I. (Jonathan R I), Krapohl, E. (Eva), Taskesen, E. (Erdogan), Hammerschlag, A.R. (Anke R.), Okbay, A. (Aysu), Zabaneh, D. (Delilah), Amin, N. (Najaf), Breen, G. (Gerome), Cesarini, D. (David), Chabris, C.F. (Christopher F), Iacono, W.G. (William), Ikram, M.A. (Arfan), Johannesson, M. (Magnus), Koellinger, P. (Philipp), Lee, J.J. (James J.), Magnusson, P.K. (Patrik), McGue, M. (Matt), Miller, M. (Mike), Ollier, W.E.R. (William), Payton, A. (Antony), Pendleton, N. (Neil), Plomin, R. (Robert), Rietveld, C.A. (Niels), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, and Posthuma, D. (Danielle)

Abstract

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta- A nalysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

Published
2017
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10. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium

Author

Stringer, S., Minica, C.C., Verweij, K.J.H., Mbarek, H., Bernard, M., Derringer, J.L., Eijk, K.R. van, Isen, J.D., Loukola, A., Maciejewski, D.F., Mihailov, E., Most, P.J. van der, Sánchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J.J., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S.D., Harris, J.M., Hartman, C.A., Henders, A.K., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Huizink, A.C., Irons, D.E., Kahn, R.S., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Lubke, G.H., Madden, P.A.F., Mägi, R., McGue, M.K., Medland, S.E., Meeus, W.H.J., Miller, M.B., Montgomery, G.W., Nivard, M.G., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Stiby, A.I., Wall, T.L., Wright, M.J., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Kaprio, J., Boks, M.P.M., Snieder, H., Spector, T., Munafò, M.R., Metspalu, A., Gelernter, J., Boomsma, D.I., Iacono, W.G., Martin, N.G., Gillespie, N.A., Derks, E.M., Vink, J.M., Stringer, S., Minica, C.C., Verweij, K.J.H., Mbarek, H., Bernard, M., Derringer, J.L., Eijk, K.R. van, Isen, J.D., Loukola, A., Maciejewski, D.F., Mihailov, E., Most, P.J. van der, Sánchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J.J., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S.D., Harris, J.M., Hartman, C.A., Henders, A.K., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Huizink, A.C., Irons, D.E., Kahn, R.S., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Lubke, G.H., Madden, P.A.F., Mägi, R., McGue, M.K., Medland, S.E., Meeus, W.H.J., Miller, M.B., Montgomery, G.W., Nivard, M.G., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Stiby, A.I., Wall, T.L., Wright, M.J., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Kaprio, J., Boks, M.P.M., Snieder, H., Spector, T., Munafò, M.R., Metspalu, A., Gelernter, J., Boomsma, D.I., Iacono, W.G., Martin, N.G., Gillespie, N.A., Derks, E.M., and Vink, J.M.

Abstract

Contains fulltext : 156357.pdf (publisher's version ) (Open Access), Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10-8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Published
2016

11. Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility

Author

Mbarek, H., Steinberg, S., Nyholt, D.R., Gordon, S.D., Miller, M.B., McRae, A.F., Hottenga, J.J., Day, F.R., Willemsen, G., Geus, E.J.C. de, Davies, G.E., Martin, H.C., Penninx, B.W.J.H., Jansen, R., McAloney, K., Vink, J.M., Kaprio, J., Plomin, R., Spector, T.D., Magnusson, P.K.E., Reversade, B., Harris, R.A., Aagaard, K., Kristjansson, R.P., Olafsson, I., Eyjolfsson, G.I., Sigurdardottir, O., Iacono, W.G., Lambalk, C.B., Montgomery, G.W., McGue, M.K., Ong, K.K., Perry, J.R.B., Martin, N.G., Stefánsson, H., Stefánsson, K., Boomsma, D.I., Mbarek, H., Steinberg, S., Nyholt, D.R., Gordon, S.D., Miller, M.B., McRae, A.F., Hottenga, J.J., Day, F.R., Willemsen, G., Geus, E.J.C. de, Davies, G.E., Martin, H.C., Penninx, B.W.J.H., Jansen, R., McAloney, K., Vink, J.M., Kaprio, J., Plomin, R., Spector, T.D., Magnusson, P.K.E., Reversade, B., Harris, R.A., Aagaard, K., Kristjansson, R.P., Olafsson, I., Eyjolfsson, G.I., Sigurdardottir, O., Iacono, W.G., Lambalk, C.B., Montgomery, G.W., McGue, M.K., Ong, K.K., Perry, J.R.B., Martin, N.G., Stefánsson, H., Stefánsson, K., and Boomsma, D.I.

Abstract

Contains fulltext : 157507.pdf (publisher's version ) (Closed access), Spontaneous dizygotic (DZ) twinning occurs in 1%–4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10−9, and rs17293443 in SMAD3, p = 1.57 × 10−8) and replicated (p = 3 × 10−3 and p = 1.44 × 10−4, respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.

Published
2016

12. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.

Abstract

Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016

13. Personality polygenes, positive affect, and life satisfaction

Author

Weiss, A. (Alexander), Baselmans, B.M.L. (Bart M. L.), Hofer, E. (Edith), Yang, J. (Jingyun), Okbay, A. (Aysu), Lind, P.A. (Penelope), Miller, M. (Mike), Nolte, I.M. (Ilja), Zhao, W. (Wei), Hagenaars, S. (Saskia), Hottenga, J.J. (Jouke Jan), Matteson, L.K. (Lindsay K.), Snieder, H. (Harold), Faul, J.D. (Jessica D.), Hartman, C.A. (C.), Boyle, P.A. (Patricia A.), Tiemeier, H.W. (Henning), Mosing, M. (Miriam), Pattie, A. (Alison), Davies, G. (Gail), Liewald, D.C.M. (David), Schmidt, R. (Reinhold), Jager, P.L. (Philip) de, Heath, A.C. (Andrew C.), Jokela, M. (Markus), Starr, J.M. (John), Oldehinkel, A.J. (Albertine), Johannesson, M. (Magnus), Cesarini, D. (David), Hofman, A. (Albert), Harris, S.E. (Sarah), Smith, J.A. (Jennifer A), Keltikangas-Järvinen, L. (Liisa), Pulkki-Råback, L. (Laura), Smith, J. (Jacqui), Iacono, W.G. (William), McGue, M. (Matt), Bennett, D.A. (David A.), Pedersen, N.L. (Nancy), Magnusson, P.K. (Patrik), Deary, I.J. (Ian), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Bartels, M. (Meike), Luciano, M. (Michelle), Weiss, A. (Alexander), Baselmans, B.M.L. (Bart M. L.), Hofer, E. (Edith), Yang, J. (Jingyun), Okbay, A. (Aysu), Lind, P.A. (Penelope), Miller, M. (Mike), Nolte, I.M. (Ilja), Zhao, W. (Wei), Hagenaars, S. (Saskia), Hottenga, J.J. (Jouke Jan), Matteson, L.K. (Lindsay K.), Snieder, H. (Harold), Faul, J.D. (Jessica D.), Hartman, C.A. (C.), Boyle, P.A. (Patricia A.), Tiemeier, H.W. (Henning), Mosing, M. (Miriam), Pattie, A. (Alison), Davies, G. (Gail), Liewald, D.C.M. (David), Schmidt, R. (Reinhold), Jager, P.L. (Philip) de, Heath, A.C. (Andrew C.), Jokela, M. (Markus), Starr, J.M. (John), Oldehinkel, A.J. (Albertine), Johannesson, M. (Magnus), Cesarini, D. (David), Hofman, A. (Albert), Harris, S.E. (Sarah), Smith, J.A. (Jennifer A), Keltikangas-Järvinen, L. (Liisa), Pulkki-Råback, L. (Laura), Smith, J. (Jacqui), Iacono, W.G. (William), McGue, M. (Matt), Bennett, D.A. (David A.), Pedersen, N.L. (Nancy), Magnusson, P.K. (Patrik), Deary, I.J. (Ian), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Bartels, M. (Meike), and Luciano, M. (Michelle)

Abstract

Copyright Â

Published
2016
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14. Genome-wide association study identifies 74 loci associated with educational attainment

Author

Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Benjamin, D.J. (Daniel J.), Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), and Benjamin, D.J. (Daniel J.)

Abstract

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Published
2016
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15. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016
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16. The genetic and environmental contributions on smoking cessation in young adults

Author

Prom-Wormley, E., Maes, H.H., Neale, M.C., Kendler, K.S., Silberg, J.L., Miles, D., Murrelle, E.L., Rhee, S.H., Corley, R.P., Hewitt, J.K., Young, S., McGue, M.K., Iacono, W.G., Legrand, L., Samek, D., Thomis, M., Boomsma, D.I., Bartels, M., Vink, J.M., Kaprio, J., Rose, R.J., Lichtenstein, P., Martin, N.G., Eaves, L.J., Prom-Wormley, E., Maes, H.H., Neale, M.C., Kendler, K.S., Silberg, J.L., Miles, D., Murrelle, E.L., Rhee, S.H., Corley, R.P., Hewitt, J.K., Young, S., McGue, M.K., Iacono, W.G., Legrand, L., Samek, D., Thomis, M., Boomsma, D.I., Bartels, M., Vink, J.M., Kaprio, J., Rose, R.J., Lichtenstein, P., Martin, N.G., and Eaves, L.J.

Abstract

Item does not contain fulltext

Published
2016

17. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

van den Berg, S.M., de Moor, M.H.M., McGue, M., Pettersson, E., Terracciano, A., Verweij, C.J.H., Amin, N., Derringer, J., Esko, T., Grootheest, G., Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., de Geus, E.J.C., Giegling, I., Gow, A. J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J., Jokela, M, Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Pulkki-Råback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J, Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Räikkönen, K., Arias-Vasquez, A., Costa, P.T., Keltikangas-Järvinen, L., van Duijn, C.M., Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Biological Psychology, Clinical Child and Family Studies, EMGO+ - Mental Health, Psychiatry, and EMGO - Mental health

Subjects
Netherlands Twin Register (NTR)
Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).

Published
2014

18. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author

Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.

Abstract

Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.

Published
2015

19. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

Author

Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi

Published
2015
Full Text
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20. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.

Abstract

Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Published
2014

21. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

Author

Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), Visscher, P.M. (Peter), Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), and Visscher, P.M. (Peter)

Abstract

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10 -15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10 -5), 3.5% (P=10 -3) and 0.5% (P=6 × 10 -5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.

Published
2014
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22. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author

Rietveld, C.A. (Niels), Esko, T. (Tõnu), Davies, G. (Gail), Pers, T.H. (Tune), Turley, P. (Patrick), Benyamin, B. (Beben), Chabris, C.F. (Christopher F.), Emilsson, V. (Valur), Johnson, A.D. (Andrew), Lee, J.J. (James J.), Leeuw, C. (Christiaan) de, Marioni, R.E. (Riccardo), Medland, S.E. (Sarah), Miller, M. (Mike), Rostapshova, O. (Olga), Lee, S.J. (Sven) van der, Vinkhuyzen, A.A.E. (Anna A.), Amin, N. (Najaf), Conley, D. (Dalton), Derringer, J., Duijn, C.M. (Cornelia) van, Fehrmann, R.S.N. (Rudolf), Franke, L. (Lude), Glaeser, E.L. (Edward L.), Hansell, N.K. (Narelle), Hayward, C. (Caroline), Iacono, W.G. (William), Ibrahim-Verbaas, C.A. (Carla), Jaddoe, V.W.V. (Vincent), Karjalainen, J. (Juha), Laibson, D. (David), Lichtenstein, P. (Paul), Liewald, D.C.M. (David), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Mcmahon, G. (George), Pedersen, N.L. (Nancy), Pinker, S. (Steven), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Rivadeneira Ramirez, F. (Fernando), Smithk, B.H. (Blair H.), Starr, J.M. (John), Tiemeier, H.W. (Henning), Timpsonm, N.J. (Nicholas J.), Trzaskowskin, M. (Maciej), Uitterlinden, A.G. (André), Verhulst, F.C. (Frank), Ward, M.E. (Mary), Wright, M.J. (Margaret), Smith, A.V. (Davey), Deary, I.J. (Ian), Johannesson, M. (Magnus), Plomin, R. (Robert), Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Esko, T. (Tõnu), Davies, G. (Gail), Pers, T.H. (Tune), Turley, P. (Patrick), Benyamin, B. (Beben), Chabris, C.F. (Christopher F.), Emilsson, V. (Valur), Johnson, A.D. (Andrew), Lee, J.J. (James J.), Leeuw, C. (Christiaan) de, Marioni, R.E. (Riccardo), Medland, S.E. (Sarah), Miller, M. (Mike), Rostapshova, O. (Olga), Lee, S.J. (Sven) van der, Vinkhuyzen, A.A.E. (Anna A.), Amin, N. (Najaf), Conley, D. (Dalton), Derringer, J., Duijn, C.M. (Cornelia) van, Fehrmann, R.S.N. (Rudolf), Franke, L. (Lude), Glaeser, E.L. (Edward L.), Hansell, N.K. (Narelle), Hayward, C. (Caroline), Iacono, W.G. (William), Ibrahim-Verbaas, C.A. (Carla), Jaddoe, V.W.V. (Vincent), Karjalainen, J. (Juha), Laibson, D. (David), Lichtenstein, P. (Paul), Liewald, D.C.M. (David), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Mcmahon, G. (George), Pedersen, N.L. (Nancy), Pinker, S. (Steven), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Rivadeneira Ramirez, F. (Fernando), Smithk, B.H. (Blair H.), Starr, J.M. (John), Tiemeier, H.W. (Henning), Timpsonm, N.J. (Nicholas J.), Trzaskowskin, M. (Maciej), Uitterlinden, A.G. (André), Verhulst, F.C. (Frank), Ward, M.E. (Mary), Wright, M.J. (Margaret), Smith, A.V. (Davey), Deary, I.J. (Ian), Johannesson, M. (Magnus), Plomin, R. (Robert), Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)

Abstract

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

Published
2014
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23. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author

Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Published
2014
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24. A comparison of twin birthweight data from Australia, the Netherlands, the United States, Japan and South Korea: are genetic and environmental variations in birthweight similar in Caucasians and East Asians?

Author

Hur, Y.M., Luciano, M., Martin, N.G., Boomsma, D.I., Iacono, W.G., McHue, M., Shin, J.S., Jun, J.K., Ooki, S., van Beijsterveldt, C.E.M., Han, J., and Biological Psychology

Subjects
Netherlands Twin Register (NTR)
Abstract

Birthweight has implications for physical and mental health in later life. Using data from Caucasian twins collected in Australia, the Netherlands and the United States, and from East Asian twins collected in Japan and South Korea, we compared the total phenotypic, genetic and environmental variances of birthweight between Caucasians and East Asians. Model-fitting analyses yielded four major findings. First, for both males and females, the total phenotypic variances of birthweight were about 45% larger in Caucasians than in East Asians. The larger phenotypic variances were mainly attributable to a greater shared environmental variance of birthweight in Caucasians (ranging from 62% to 67% of variance) than Asians (48% to 53%). Second, the genetic variance of birthweight was equal in Caucasians and East Asians for both males and females, explaining a maximum of 17% of variance. Third, small variations in total phenotypic variances of birthweight within Caucasians and within East Asians were mainly due to differences in nonshared environmental variances. We speculate that maternal effects (both genetic and environmental) explain the large shared environmental variance in birthweight and may account for the differences in phenotypic variance in birthweight between Caucasians and East Asians. Recent molecular findings and specific environmental factors that are subsumed by maternal effects are discussed.

Published
2005

27. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

Author

LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., Koellinger, P.D., LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., and Koellinger, P.D.

Abstract

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

Published
2013

28. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment

Author

Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)

Published
2013
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29. A Twin Study of the Genetics of High Cognitive Ability Selected from 11,000 Twin Pairs in Six Studies from Four Countries

Author

Haworth, C.M.A., Wright, M.J., Martin, N.W., Martin, N.G., Boomsma, D.I., Bartels, M., Posthuma, D., Davis, O.S.P., Brant, A.M., Corley, R.P., Hewitt, J.K., Iacono, W.G., McGue, M., Thompson, L.A., Hart, S.A., Petrill, S.A., Lubinski, D., Plomin, R., Haworth, C.M.A., Wright, M.J., Martin, N.W., Martin, N.G., Boomsma, D.I., Bartels, M., Posthuma, D., Davis, O.S.P., Brant, A.M., Corley, R.P., Hewitt, J.K., Iacono, W.G., McGue, M., Thompson, L.A., Hart, S.A., Petrill, S.A., Lubinski, D., and Plomin, R.

Abstract

Although much genetic research has addressed normal variation in intelligence, little is known about the etiology of high cognitive abilities. Using data from 11,000 twin pairs (age range = 6-71 years) from the genetics of high cognitive abilities consortium, we investigated the genetic and environmental etiologies of high general cognitive ability (g). Age-appropriate psychometric cognitive tests were administered to the twins and used to create g scores standardized within each study. Liability-threshold model fitting was used to estimate genetic and environmental parameters for the top 15% of the distribution of g. Genetic influence for high g was substantial (0.50, with a 95% confidence interval of 0.41-0.60). Shared environmental influences were moderate (0.28, 0.19-0.37). We conclude that genetic variation contributes substantially to high g in Australia, the Netherlands, the United Kingdom and the United States. © 2009 Springer Science+Business Media, LLC.

Published
2009
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30. Genetic influences on the difference in variability of height, weight and body mass index between Caucasian and East Asian adolescent twins.

Author

Hur, Y.M., Kaprio, J., Iacono, W.G., Boomsma, D.I., McGue, M., Silventoinen, K., Martin, N.G., Luciano, M., Visscher, P.M., Rose, R.J., He, M., Ando, J., Ooki, S., Nonaka, K., Lin, C.C.H., Lajunen, H.R., Cornes, B.K., Bartels, M., van Beijsterveldt, C.E.M., Cherny, S.S., Mitchell, K., Hur, Y.M., Kaprio, J., Iacono, W.G., Boomsma, D.I., McGue, M., Silventoinen, K., Martin, N.G., Luciano, M., Visscher, P.M., Rose, R.J., He, M., Ando, J., Ooki, S., Nonaka, K., Lin, C.C.H., Lajunen, H.R., Cornes, B.K., Bartels, M., van Beijsterveldt, C.E.M., Cherny, S.S., and Mitchell, K.

Abstract

Objective: Twin studies are useful for investigating the causes of trait variation between as well as within a population. The goals of the present study were two-fold: First, we aimed to compare the total phenotypic, genetic and environmental variances of height, weight and BMI between Caucasians and East Asians using twins. Secondly, we intended to estimate the extent to which genetic and environmental factors contribute to differences in variability of height, weight and BMI between Caucasians and East Asians. Design: Height and weight data from 3735 Caucasian and 1584 East Asian twin pairs (age: 13-15 years) from Australia, China, Finland, Japan, the Netherlands, South Korea, Taiwan and the United States were used for analyses. Maximum likelihood twin correlations and variance components model-fitting analyses were conducted to fulfill the goals of the present study. Results: The absolute genetic variances for height, weight and BMI were consistently greater in Caucasians than in East Asians with corresponding differences in total variances for all three body measures. In all 80 to 100% of the differences in total variances of height, weight and BMI between the two population groups were associated with genetic differences. Conclusion: Height, weight and BMI were more variable in Caucasian than in East Asian adolescents. Genetic variances for these three body measures were also larger in Caucasians than in East Asians. Variance components model-fitting analyses indicated that genetic factors contributed to the difference in variability of height, weight and BMI between the two population groups. Association studies for these body measures should take account of our findings of differences in genetic variances between the two population groups. © 2008 Macmillan Publishers Limited All rights reserved.

Published
2008
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43. Habituation of the Skin Conductance Response to Strong Stimuli: A Twin Study.

Author

Lykken, D.T., Iacono, W.G., Haroian, K., McGue, M., and Bouchard Jr., T.J.

Subjects
*GALVANIC skin response, *REFLEXES, *STIMULUS intensity, *SENSORY perception
Abstract

Skin conductance responses to a series of loud tones were measured bilaterally in 121 pairs of adult twins, 53 pairs reared together and 68 pairs reared apart. Subjects were given an absorbing task on which to focus their attention and instructed to ignore the meaningless tones. Range-correction eliminated hand and sex differences in SCR amplitude and also the correlation with age of this variable. For the combined group of 79 pairs of monozygotic (MZ) twins, the within-pair correlations for V-intercept, the slope of the habituation curve, and the number of trials to habituation were near the limits of retest reliability for these variables. After range-correction, the correlation for V-intercept for the 42 pairs of dizygotic (DZ) twins was about half the MZ value, suggesting that initial electrodermal reactivity is strongly genetic and can be interpreted according to a polygenic-additive model. Biometric model testing indicated that stable individual differences in uncorrected SCR amplitude and in habituation slope are primarily determined by non-additive genetic factors. About 40% of the total variance (and most of the stable variance) in number of trials to habituation is genetically determined. Co-twins of MZ twins who were electrodermal nonresponders tended also to be hyporesponsive while co-twins of DZ nonresponders tended to be normo-responsive. [ABSTRACT FROM AUTHOR]

Published
1988
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50. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Author

Polderman, T.J.C., Stefansson, K., Zuccolo, L., Wall, T.L., Stan����kov��, A., Zhan, X., Hunter, D.J., Davila-Velderrain, J., Palviainen, T., Brazel, D.M., 23andMe Research Team, Haller, T., Chen, F., Jiang, Y., Johnson, E.O., Rose, R.J., Martin, N.G., Wedow, R., Rice, J.P., Boehnke, M., Jorgenson, E., Posthuma, D., Haessler, J., Kellis, M., Young, K.A., Jansen, P.R., Bjornsdottir, G., Kardia, S.L.R., Metspalu, A., Chen, C., Eaton, C.B., Madden, P.A.F., Gillespie, N.A., McGue, M., Choquet, H., McMahon, G., Jang, S.-K., Faul, J.D., Nielsen, J.B., Fritsche, L.G., Yin, J., Cucca, F., Medland, S.E., Vrieze, S., Thorgeirsson, T.E., Loukola, A., Reginsson, G.W., Tian, C., Orr��, V., HUNT All-In Psychiatry, Iacono, W.G., Gordon, S.D., Kraft, P., Fiorillo, E., Reiner, A.P., Willer, C.J., Boomsma, D.I., Munaf��, M.R., Tyrfingsson, T., Kaprio, J., Laakso, M., Zajac, G.J.M., Willemsen, G., Hickie, I.B., Runarsdottir, V., Li, Y., Hottenga, J.-J., McQueen, M.B., Ehringer, M.A., Zhou, W., Smith, J.A., Taylor, A.E., Tindle, H.A., Kooperberg, C., Boardman, J.D., Lee, J.J., McGuire, D., Zhao, W., Mulas, A., Cornelis, M.C., Lind, P.A., Hveem, K., Weisner, C., Datta, G., Gudbjartsson, D.F., Lutz, S.M., M��gi, R., Hewitt, J.K., Turman, C., Thai, K.K., Stallings, M.C., Kamatani, Y., Hopfer, C.J., David, S.P., Young, H., Rimm, E., Bierut, L.J., Ling, Y., Foerster, J.R., Harris, K.M., Davies, G.E., Krauter, K.S., Matoba, N., Abecasis, G., Esko, T., Keller, M.C., Whitfield, J.B., Liu, D.J., Huang, H., Stitzel, J.A., Liu, M., Peters, U., Saccone, N.L., Docherty, A.R., Pandit, A., Stefansson, H., Hokanson, J.E., Heath, A.C., Okada, Y., Weir, D.R., and Mohlke, K.L.

Subjects
3. Good health
Abstract

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

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